SPID#: 10 To investigate the basis for asymptomatic SIV infection in naturally- infected sooty mangabey monkeys and African green monkeys, quantitative- competitive PCR (QC-PCR) (to measure viral load) assays were developed for SIVsmm and SIVagm and the SIVsmm-related virus SIVmac that induces AIDS in rhesus macaques. Interestingly, naturally infected, healthy sooty mangabeys display levels of active SIV replication that equal, and in some cases exceed, those seen in macaques suffering from advanced SIV- induced immunodeficiency. Similarly, SIV-infected African green monkeys demonstrate chronically high levels of plasma viremia. SIV-infected sooty mangabeys have no demonstrable CTL activity against virus expressing cells, and a low titer and antigenically restricted humoral antiviral immune response. The antiviral CTL response of African green monkeys has not been studied, but a similar humoral immune response is seen in infected animals. That SIV replication proceeds at high levels without CD4 depletion and the finding of histologically normal lymphoid tissues in infected animals indicates that the interaction of virus with sooty mangabey host cells is not cytopathic. Results from tissue culture studies support this conclusion, and ongoing studies are focused on elucidating the basis for this lack of cytopathicity. The evolution of SIVsmm and SIVagm in their natural hosts may have selected for a non- cytophatic course of virus infection of host cells, and a limited or absent antiviral immune response. In species that are not natural hosts for T cell-tropic lentiviruses, and where the virus infection has direct cytopathic consequences, including rhesus macaques and humans, the character of the antiviral immune response may determine the rate of disease progression seen following virus infection, and if incompletely effective, may potentially contribute to immune system compromise.